tbuckley/cabot-search huggingface dataset:
A Novel Robotic Bronchoscope System for Navigation and Biopsy of Pulmonary Lesions
Authors: Xingguang Duan, Dongsheng Xie, Runtian Zhang, Xiaotian Li, Jiali Sun, Chao Qian, Xinya Song, Changsheng Li
Journal: Cyborg and Bionic Systems (2023)

Transbronchial biopsy sampling, as a minimally invasive method with relatively low risk, has been proved to be a promising treatment in the field of respiratory surgery. Although several robotic bronchoscopes have been developed, it remains a great challenge to balance size and flexibility, while integrating multisensors to realize navigation during complex airway networks. This paper proposes a novel robotic bronchoscope system composed by end effector with relatively small size, relevant actuation unit, and navigation system with path planning and surgical guidance capability. The main part of the end effector is machined by bidirectional groove on a nickel-titanium tube, which can realize bending, rotation, and translation 3 degrees of freedom. A prototype of the proposed robotic bronchoscope system is designed and fabricated, and its performance is tested through several experiments to verify the stiffness, flexibility, and navigation performance. The results show that the proposed system is with good environment adaptiveness, and it can become a promising biopsy method through natural cavity of the human body.
Tuned activation of MSLN-CAR T cells induces superior antitumor responses in ovarian cancer models
Authors: Esther Schoutrop, Thomas Poiret, Ibrahim El-Serafi, Ying Zhao, Rui He, Alina Moter, Johan Henriksson, Moustapha Hassan, Isabelle Magalhaes, Jonas Mattsson
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Limited persistence of functional CAR T cells in the immunosuppressive solid tumor microenvironment remains a major hurdle in the successful translation of CAR T cell therapy to treat solid tumors. Fine-tuning of CAR T cell activation by mutating CD3ζ chain immunoreceptor tyrosine-based activation motifs (ITAMs) in CD19-CAR T cells (containing the CD28 costimulatory domain) has proven to extend functional CAR T cell persistence in preclinical models of B cell malignancies. Methods In this study, two conventional second-generation MSLN-CAR T cell constructs encoding for either a CD28 co-stimulatory (M28z) or 4-1BB costimulatory (MBBz) domain and a novel mesothelin (MSLN)-directed CAR T cell construct encoding for the CD28 costimulatory domain and CD3ζ chain containing a single ITAM (M1xx) were evaluated using in vitro and in vivo preclinical models of ovarian cancer. Two ovarian cancer cell lines and two orthotopic models of ovarian cancer in NSG mice were used: SKOV-3 cells inoculated through microsurgery in the ovary and to mimic a disseminated model of advanced ovarian cancer, OVCAR-4 cells injected intraperitoneally. MSLN-CAR T cell treatment efficacy was evaluated by survival analysis and the characterization and quantification of the different MSLN-CAR T cells were performed by flow cytometry, quantitative PCR and gene expression analysis. Results M1xx CAR T cells elicited superior antitumor potency and persistence, as compared with the conventional second generation M28z and MBBz CAR T cells. Ex vivo M28z and MBBz CAR T cells displayed a more exhausted phenotype than M1xx CAR T cells as determined by co-expression of PD-1, LAG-3 and TIM-3. Furthermore, M1xx CAR T cells showed superior ex vivo IFNy, TNF and GzB production and were characterized by a self-renewal gene signature. Conclusions Altogether, our study demonstrates the enhanced therapeutic potential of MSLN-CAR T cells expressing a mutated CD3ζ chain containing a single ITAM for the treatment of ovarian cancer. CAR T cells armored with calibrated activation potential may improve the clinical responses in solid tumors.
A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration
Authors: Timothy L Jackson, Jason Slakter, Marc Buyse, Kun Wang, Pravin U Dugel, Charles C Wykoff, David S Boyer, Michael Gerometta, Megan E Baldwin, Clare F Price
Journal: Ophthalmology (2023)

Neovascular (wet) age-related macular degeneration (nAMD) is driven by VEGFs A, C, and D, which promote angiogenesis and vascular permeability. Intravitreal injections of anti-VEGF-A drugs are the standard of care, but these do not inhibit VEGF-C and D, which may explain why many patients fail to respond fully. This trial aimed to test the safety and efficacy of OPT-302, a biologic inhibitor of VEGF-C and D, in combination with the anti-VEGF-A inhibitor ranibizumab.Dose-ranging, phase 2b, randomized, double-masked, sham-controlled trial.Participants with treatment-naive nAMD were enrolled from 109 sites across Europe, Israel, and the United States.Participants were randomized to 6, 4-weekly, intravitreal injections of 0.5 mg OPT-302, 2.0 mg OPT-302, or sham, plus intravitreal 0.5 mg ranibizumab.The primary outcome was mean change in ETDRS best-corrected visual acuity (BCVA) at 24 weeks. Secondary outcomes (comparing baseline with week 24) were the proportion of participants gaining or losing ≥ 15 ETDRS BCVA letters; area under the ETDRS BCVA over time curve; change in spectral-domain OCT (SD-OCT) central subfield thickness; and change in intraretinal fluid and subretinal fluid on SD-OCT.Of 366 participants recruited from December 1, 2017, to November 30, 2018, 122, 123, and 121 were randomized to 0.5 mg OPT-302, 2.0 mg OPT-302, and sham, respectively. Mean (± standard deviation) visual acuity gain in the 2.0 mg OPT-302 group was significantly superior to sham (+14.2 ± 11.61 vs. +10.8 ± 11.52 letters; P = 0.01). The 0.5 mg OPT-302 group was not significantly different than the sham group (+9.44 ± 11.32 letters; P = 0.83). Compared with sham, the secondary BCVA outcomes favored the 2.0 mg OPT-302 group, with structural outcomes favoring both OPT-302 dosage groups. Adverse events (AEs) were similar across groups, with 16 (13.3%), 7 (5.6%), and 10 (8.3%) participants in the lower-dose, higher-dose, and sham groups, respectively, developing at least 1 serious AE. Two unrelated deaths both occurred in the sham arm.Significantly superior vision gain was observed with OPT-302 2.0 mg combination therapy, versus standard of care, with favorable safety (ClinicalTrials.gov identifier: NCT03345082).Proprietary or commercial disclosure may be found after the references.
Dietary patterns and cardiometabolic health: Clinical evidence and mechanism
Authors: Wenting Wang, Yanfei Liu, Yiwen Li, Binyu Luo, Zhixiu Lin, Keji Chen, Yue Liu
Journal: MedComm (2023)

Abstract For centuries, the search for nutritional interventions to underpin cardiovascular treatment and prevention guidelines has contributed to the rapid development of the field of dietary patterns and cardiometabolic disease (CMD). Numerous studies have demonstrated that healthy dietary patterns with emphasis on food‐based recommendations are the gold standard for extending lifespan and reducing the risks of CMD and mortality. Healthy dietary patterns include various permutations of energy restriction, macronutrients, and food intake patterns such as calorie restriction, intermittent fasting, Mediterranean diet, plant‐based diets, etc. Early implementation of healthy dietary patterns in patients with CMD is encouraged, but an understanding of the mechanisms by which these patterns trigger cardiometabolic benefits remains incomplete. Hence, this review examined several dietary patterns that may improve cardiometabolic health, including restrictive dietary patterns, regional dietary patterns, and diets based on controlled macronutrients and food groups, summarizing cutting‐edge evidence and potential mechanisms for CMD prevention and treatment. Particularly, considering individual differences in responses to dietary composition and nutritional changes in organ tissue diversity, we highlighted the critical role of individual gut microbiota in the crosstalk between diet and CMD and recommend a more precise and dynamic nutritional strategy for CMD by developing dietary patterns based on individual gut microbiota profiles.
Association Between Opioid Tapering and Subsequent Health Care Use, Medication Adherence, and Chronic Condition Control
Authors: Elizabeth M. Magnan, Daniel J. Tancredi, Guibo Xing, Alicia Agnoli, Anthony Jerant, Joshua J. Fenton
Journal: JAMA Network Open (2023)

Importance Opioid tapering has been associated with negative consequences, such as increased overdoses and mental health needs. Tapering could also alter use of health care services and worsen care of comorbid conditions through disruption in primary care. Objective To evaluate tapering of stable long-term opioid therapy (LTOT) and subsequent health care service use and chronic condition care. Design, Setting, and Participants A retrospective cohort study was conducted from January 1, 2008, to December 31, 2019. Data analysis was performed from July 9, 2020, to December 9, 2022. Data from the Optum Labs Data Warehouse, which contains deidentified retrospective administrative claims data and linked electronic health record data for commercial and Medicare Advantage enrollees, were used. Adults aged 18 years or older prescribed stable doses of LTOT at 50 morphine milligram equivalents or more per day during a 12-month baseline period were included, including subcohorts with hypertension or diabetes. Exposures Opioid tapering, with 15% or more relative reduction in mean daily dose in 6 overlapping periods during 6 months. Main Outcomes and Measures Emergency department visits, hospitalizations, primary care and specialist visits, antihypertensive or antiglycemic medication adherence, and blood pressure and hemoglobin A 1c levels during up to 12 months’ follow-up. Covariates included sociodemographic characteristics, comorbidities, health care use, and chronic condition control. Results Among 113 604 patients (60 764 [53.5%] women; mean [SD] age, 58.1 [11.8] years) prescribed LTOT, 41 207 had hypertension and 23 335 had diabetes; in all cohorts, approximately half were women, and half were aged 50 to 65 years. In the overall cohort, tapering was associated with more emergency department visits (adjusted incidence rate ratio [aIRR], 1.19; 95% CI, 1.16-1.21) and hospitalizations (aIRR, 1.16; 95% CI, 1.12-1.20), with similar magnitude associations in the hypertension and diabetes subcohorts. Tapering was associated with fewer primary care visits in the overall cohort (aIRR, 0.95; 95% CI, 0.94-0.96) and hypertension subcohort (aIRR, 0.98; 95% CI, 0.97-0.99). For the hypertension or diabetes subcohorts, tapering was associated with reduced medication adherence (hypertension: aIRR, 0.60; 95% CI, 0.59-0.62; diabetes: aIRR, 0.69; 95% CI, 0.67-0.71) and small increases in diastolic blood pressure and hemoglobin A 1c level. Conclusions and Relevance In this cohort study of patients prescribed LTOT, opioid tapering was associated with more emergency department visits and hospitalizations, fewer primary care visits, and reduced antihypertensive and antidiabetic medication adherence. These outcomes may represent unintended negative consequences of opioid tapering for policy makers and clinicians to consider.
Prone Positioning Improved Ventilation-Perfusion Matching in Severe Pediatric Acute Respiratory Distress Syndrome
Authors: Long Xiang, Hong Ren, Ying Wang, Zhulin Wang, Inéz Frerichs, Zhanqi Zhao
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Prone Positioning Improved Ventilation-Perfusion Matching in Severe Pediatric Acute Respiratory Distress Syndrome." American Journal of Respiratory and Critical Care Medicine, 207(10), pp. e75–e76
SARS-CoV-2 Results in Self-collected Nasal Swabs vs Swabs Collected by Health Care Workers in Children and Adolescents—Reply
Authors: Jesse J. Waggoner, Erika A. Tyburski, Wilbur A. Lam
Journal: JAMA (2023)

In Reply We appreciate the letter from Drs Hong and Sung about our study,1 which demonstrated the ability of children and adolescents to self-collect samples for respiratory virus testing and independently participate in their medical care.
Visitation
Authors: Elane Kim
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Vaccination, Acute Myocardial Infarction, and Ischemic Stroke After COVID-19 Infection—Reply
Authors: Kyungmin Huh, Young-Eun Kim, Jaehun Jung
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Circulation of Rhinoviruses and/or Enteroviruses in Pediatric Patients With Acute Respiratory Illness Before and During the COVID-19 Pandemic in the US
Authors: Danielle A. Rankin, Andrew J. Spieker, Ariana Perez, Anna L. Stahl, Herdi K. Rahman, Laura S. Stewart, Jennifer E. Schuster, Joana Y. Lively, Zaid Haddadin, Varvara Probst, Marian G. Michaels, John V. Williams, Julie A. Boom, Leila C. Sahni, Mary A. Staat, Elizabeth P. Schlaudecker, Monica M. McNeal, Christopher J. Harrison, Geoffrey A. Weinberg, Peter G. Szilagyi, Janet A. Englund, Eileen J. Klein, Susan I. Gerber, Meredith McMorrow, Brian Rha, James D. Chappell, Rangaraj Selvarangan, Claire M. Midgley, Natasha B. Halasa, Mary Moffatt, Gina Weddle, Bonnie Strelitz, Kristen Lacombe, Chelsea Rohlfs
Journal: JAMA Network Open (2023)

Rhinoviruses and/or enteroviruses, which continued to circulate during the COVID-19 pandemic, are commonly detected in pediatric patients with acute respiratory illness (ARI). Yet detailed characterization of rhinovirus and/or enterovirus detection over time is limited, especially by age group and health care setting.
Vaccination, Acute Myocardial Infarction, and Ischemic Stroke After COVID-19 Infection
Authors: Wei-Min Chu, Chi-Yen Wang, James Cheng-Chung Wei
Journal: JAMA (2023)

To the Editor We would like to highlight some key points about the recent article that reported that patients who received full vaccination against COVID-19 had a reduced risk of acute myocardial infarction (AMI) and ischemic stroke after COVID-19 diagnosis.1
Comprehensive Associations between Acidosis and the Skeleton in Patients with Kidney Disease
Authors: Rebecca V. Levy, Donald J. McMahon, Sanchita Agarwal, David Dempster, Hua Zhou, Barbara M. Misof, X.E. Guo, Mafo Kamanda-Kosseh, Maria Alejandra Aponte, Kimberly Reidy, Juhi Kumar, Maria Fusaro, Denver D. Brown, Michal L. Melamed, Thomas L. Nickolas
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Renal osteodystrophy (ROD) contributes substantially to morbidity in CKD, including increased fracture risk. Metabolic acidosis (MA) contributes to the development of ROD, but an up-to-date skeletal phenotype in CKD-associated acidosis has not been described. We comprehensively studied associations between acidosis and bone in patients with CKD using advanced methods to image the skeleton and analyze bone-tissue, along with biochemical testing. Cross-sectionally, acidosis was associated with higher markers of bone remodeling and female-specific impairments in cortical and trabecular bone quality. Prospectively, acidosis was associated with cortical expansion and trabecular microarchitectural deterioration. At the bone-tissue level, acidosis was associated with deficits in bone mineral content. Future work investigating acidosis correction on bone quality is warranted. Background: Renal osteodystrophy is a state of impaired bone quality and strength. Metabolic acidosis (MA) is associated with alterations in bone quality including remodeling, microarchitecture, and mineralization. No studies in patients with CKD have provided a comprehensive multimodal skeletal phenotype of MA. We aim to describe the structure and makeup of bone in patients with MA in the setting of CKD using biochemistry, noninvasive imaging, and histomorphometry. Methods: The retrospective cross-sectional analyses included 180 patients with CKD. MA was defined as bicarbonate ≤22 mEq/L. We evaluated circulating bone turnover markers and skeletal imaging with dual energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subset of 54 participants had follow-up. We assessed associations between baseline and change in bicarbonate with change in bone outcomes. Histomorphometry, microCT, and quantitative backscatter electron microscopy assessed bone biopsy outcomes in 22 participants. Results: The mean age was 68±10 years, 54% of participants were male, and 55% were White. At baseline, acidotic subjects had higher markers of bone turnover, lower areal bone mineral density at the radius by dual energy x-ray absorptiometry, and lower cortical and trabecular volumetric bone mineral density and impaired trabecular microarchitecture. Over time, acidosis was associated with opposing cortical and trabecular effects: cortical expansion but trabecular deterioration. Bone-tissue analyses showed reduced tissue mineral density with increased heterogeneity of calcium distribution in acidotic participants. Conclusions: MA is associated with multiple impairments in bone quality. Future work should examine whether correction of acidosis improves bone quality and strength in patients with CKD.
Macrophages promote anti-androgen resistance in prostate cancer bone disease
Authors: Xue-Feng Li, Cigdem Selli, Han-Lin Zhou, Jian Cao, Shuiqing Wu, Ruo-Yu Ma, Ye Lu, Cheng-Bin Zhang, Bijie Xun, Alyson D. Lam, Xiao-Cong Pang, Anu Fernando, Zeda Zhang, Asier Unciti-Broceta, Neil O. Carragher, Prakash Ramachandran, Neil C. Henderson, Ling-Ling Sun, Hai-Yan Hu, Gui-Bo Li, Charles Sawyers, Bin-Zhi Qian
Journal: The Journal of Experimental Medicine (2023)

Metastatic castration-resistant prostate cancer (PC) is the final stage of PC that acquires resistance to androgen deprivation therapies (ADT). Despite progresses in understanding of disease mechanisms, the specific contribution of the metastatic microenvironment to ADT resistance remains largely unknown. The current study identified that the macrophage is the major microenvironmental component of bone-metastatic PC in patients. Using a novel in vivo model, we demonstrated that macrophages were critical for enzalutamide resistance through induction of a wound-healing–like response of ECM–receptor gene expression. Mechanistically, macrophages drove resistance through cytokine activin A that induced fibronectin (FN1)-integrin alpha 5 (ITGA5)–tyrosine kinase Src (SRC) signaling cascade in PC cells. This novel mechanism was strongly supported by bioinformatics analysis of patient transcriptomics datasets. Furthermore, macrophage depletion or SRC inhibition using a novel specific inhibitor significantly inhibited resistant growth. Together, our findings elucidated a novel mechanism of macrophage-induced anti-androgen resistance of metastatic PC and a promising therapeutic approach to treat this deadly disease.
Correction: Prolyl-tRNA synthetase as a novel therapeutic target in multiple myeloma
Authors: Keiji Kurata, Anna James-Bott, Mark A. Tye, Leona Yamamoto, Mehmet K. Samur, Yu-Tzu Tai, James Dunford, Catrine Johansson, Filiz Senbabaoglu, Martin Philpott, Charlotte Palmer, Karthik Ramasamy, Sarah Gooding, Mihaela Smilova, Giorgia Gaeta, Manman Guo, John C. Christianson, N. Connor Payne, Kritika Singh, Kubra Karagoz, Matthew E. Stokes, Maria Ortiz, Patrick Hagner, Anjan Thakurta, Adam Cribbs, Ralph Mazitschek, Teru Hideshima, Kenneth C. Anderson, Udo Oppermann
Journal: Blood Cancer Journal (2023)
Is it bad, is it good, or is IgG4 just misunderstood?
Authors: Shiv Pillai
Journal: Science Immunology (2023)

Repeated doses of mRNA vaccines for COVID-19 result in increased proportions of anti-spike antibodies of the IgG4 subclass, which are known to neutralize well and to form mixed immune complexes with IgG1 but, in a pure form, might be less effective than IgG1 or IgG3 antibodies in facilitating opsonization by phagocytes, complement fixation, and NK cell-dependent elimination of infected cells (see related Research Article by Irrgang et al.).